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斑马鱼化学诱导性骨关节炎模型的表征

Characterization of a chemically induced osteoarthritis model in zebrafish.

作者信息

Xiao Gongyi, Qin Jin, Yang Huiping, Song Qizhi, Zhang Ruobin, Huang Junlan, Mou Yuexi, Liu Wen, Sun Xianding, Nie Mao

机构信息

Center for Joint Surgery, Department of Orthopedic Surgery, The Second Affiliated Hospital of Chongqing Medical University, 74 Linjiang Road, Chongqing, 400010, China.

Department of Orthopedic Surgery, Chonggang General Hospital, No. 1 Dayan Sancun, Dadukou District, Chongqing, 400000, China.

出版信息

Sci Rep. 2025 Jan 31;15(1):3905. doi: 10.1038/s41598-025-88125-x.

DOI:10.1038/s41598-025-88125-x
PMID:39890962
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11785742/
Abstract

Osteoarthritis (OA) is characterized by the progressive degeneration of the synovial joint, leading to irreversible damage to articular cartilage and subchondral bone. While animal models have advanced our understanding of OA, numerous unresolved issues still remain. The zebrafish, known for its transparent body, rapid developmental, and impressive regenerative capabilities, offers substantial potential for osteoarthritis research. This study seeks to establish a new OA model utilizing the zebrafish jaw joint, acting as a supplement to traditional animal models. In the future, this model could serve as a valuable platform for delving deeper into the mechanisms of this disease, as well as for advancing drug discovery and therapeutic interventions. Leveraging the skeletal structure of zebrafish, we targeted the largest jaw joint for our research. A custom fixation device was crafted, and a microinjection system was utilized to inject mono-iodoacetate (MIA) or collagenase type II (CTII) into the joint cavity of zebrafish. Subsequent analyses included histological staining, immunohistochemistry, OA research society international (OARSI) scoring, and real-time in vivo imaging were performed at 7, 14, and 28 days post injection. Our results effectively demonstrated the presence of synovial inflammation and cartilage damage within the zebrafish mandible, affirming the feasibility of inducing OA in zebrafish. In conclusion, the local injection of chemical agents into the joint cavity of zebrafish effectively induced the occurrence of OA. Establishing the zebrafish OA model enhances the array of animal models available for OA research. Moreover, zebrafish present distinct advantages, including robust regenerative abilities, genetic editing simplicity, and efficient drug screening. Consequently, this offers a fresh avenue for investigating the pathogenesis, prevention, and potential therapeutic approaches for human OA.

摘要

骨关节炎(OA)的特征是滑膜关节进行性退变,导致关节软骨和软骨下骨的不可逆损伤。虽然动物模型增进了我们对骨关节炎的理解,但仍有许多未解决的问题。斑马鱼以其透明的身体、快速的发育和令人印象深刻的再生能力而闻名,为骨关节炎研究提供了巨大潜力。本研究旨在利用斑马鱼颌关节建立一种新的骨关节炎模型,作为传统动物模型的补充。未来,该模型可作为一个有价值的平台,用于更深入地研究这种疾病的机制,以及推进药物发现和治疗干预。利用斑马鱼的骨骼结构,我们将最大的颌关节作为研究目标。制作了一个定制的固定装置,并利用微注射系统将单碘乙酸盐(MIA)或II型胶原酶(CTII)注射到斑马鱼的关节腔中。后续分析包括组织学染色、免疫组织化学、国际骨关节炎研究学会(OARSI)评分,并在注射后7天、14天和28天进行实时体内成像。我们的结果有效地证明了斑马鱼下颌骨内存在滑膜炎症和软骨损伤,证实了在斑马鱼中诱导骨关节炎的可行性。总之,向斑马鱼关节腔内局部注射化学试剂可有效诱导骨关节炎的发生。建立斑马鱼骨关节炎模型增加了可用于骨关节炎研究的动物模型种类。此外,斑马鱼具有明显的优势,包括强大的再生能力、简单的基因编辑和高效的药物筛选。因此,这为研究人类骨关节炎的发病机制、预防和潜在治疗方法提供了一条新途径。

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本文引用的文献

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Current Status of the Zebrafish Euthanasia and Humane Endpoint in the Republic of Korea and Guideline Suggestion from Nationwide Expert Elicitation: A Model for Other Countries.韩国斑马鱼安乐死和人道终点的现状及全国专家征集的指导建议:为其他国家提供的模式。
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Osteomodulin downregulation is associated with osteoarthritis development.
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Osteoarthritis Pain.骨关节炎疼痛。
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What Is Osteoarthritis?什么是骨关节炎?
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Nat Rev Rheumatol. 2022 May;18(5):258-275. doi: 10.1038/s41584-022-00749-9. Epub 2022 Feb 14.
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Regeneration of Jaw Joint Cartilage in Adult Zebrafish.成年斑马鱼颌关节软骨的再生
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OA foundations - experimental models of osteoarthritis.骨关节炎的基础——骨关节炎的实验模型
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